We identified a gene environment interaction between DRD1 and secondhand smoke in relation to lung cancer risk--an observation that was seen in ever and never smokers. While dopamine signaling and its receptors are well characterized in the brain, there is a paucity of data regarding the role and the expression pattern of dopamine and its receptors in the normal lung. Previous studies have shown that dopamine plays an important role in bronchi-dilation and respiration, however a comprehensive analysis of dopamine, its receptors, transporters and metabolism has not been conducted. We are therefore mapping the dopamine axis in both normal lung tissue and human lung cancer. Our initial studies suggest that certain subtypes of the dopamine receptor family may function as tumor suppressors and we are currently validating those observations and investigating the molecular mechanism. In addition, we are examining the efficacy of specific dopamine receptor agonists and antagonists as therapeutic agents against cancer and analyzing the key mechanistic pathways involved.